This research will demonstrate that the fate of ischemic myocardium is determined, in large part, by the conditions under which blood supply is restored. Using an experimental model of acute regional ischemia (left anterior descending coronary artery ligation), we will characterize the structural, functional and metabolic consequences of reperfusion damage which can be avoided by controlling the conditions under which blood supply is restored (i.e. temperature, composition, and myocardial energy demands). These studies will: a) explain why streptokinase thrombolysis with normal blood reperfusion fails to restore myocardial function, b) demonstrate how surgical revascularization (CABG) with blood cardioplegic reperfusion salvages heart muscle and restores function despite a greater delay between diagnosis and revascularization; and c) present a new method for delivering regional blood cardioplegia in a working heart in the catheterization lab setting which may lead to a new treatment of acute myocardial infarction whereby regional cardiopelgia will be added to streptokinase thrombolysis. Additional studies will focus upon the critical role of the non-ischemic myocardium in causing cardiogenic shock in patients with acute myocardial infarction. These studies may lead to earlier operations for patients in cardiogenic shock and an altered operative strategy in patients with extending myocardial infarctions whereby cardioplegic protective efforts will be directed principally towards the non-ischemic myocardium responsible for carrying the hemodynamic burden. Finally, studies will employ a globally ischemic model for severe energy depletion before aortic clamping to simulate operating conditions in patients with advanced cardiac disease. This aspect of the research will show how the period of cardioplegic induction can be used as a time of active resuscitation of damage hearts which must undergo subsequent prolonged aortic clamping.